Remarkable alterations in the regulation of water and saline intake have been noted in animals with lesions in the dorsal hindbrain. More recently, studies indicate that lesions placed in the area postrema/adjacent nucleus of the solitary tract result in greatly increased consumption of water and saline. Moreover, very similar changes in water intake are noted after lesions that include the lateral parabrachial nucleus, a pontine nucleus that receives direct input from the area postrema and nucleus of the solitary tract. These observations suggest that the area postrema and nucleus of the solitary tract in the medulla and the lateral parabrachial nucleus in the pons are components of an ascending inhibitory system that acts to inhibit the consumption of fluids to replenish the extracellular fluid compartment. The nature of inhibitory signals in this pathway or the precise site(s) at which they might act have yet to be elucidated. Thus, a careful examination of the dorsomedial hindbrain and its projection sites is necessary to develop our understanding of the mechanisms involved in the control of water and electrolyte balance. The studies presented here will examine several aspects of this proposed inhibitory hindbrain pathway. Experiment 1 will examine the specific role of the nucleus of the solitary tract in this inhibitory pathway. Experiment 2 will examine the functional interaction between the area postrema, nucleus of the solitary tract and lateral parabrachial nucleus in this pathway. Experiment 3 will examine the pharmacology of the projections from the area postrema/nucleus of the solitary tract to the lateral parabrachial nucleus. Finally, experiment 4 will study the possibility that information from atrial receptors is disrupted by these lesions. The present research plan will examine the proposed hindbrain inhibitory pathway using a variety of methods including behavioral, physiological, pharmacological and anatomical analyses. Since many of these methods, such as 3 dimensional image analysis, have only recently become available, these studies will provide fundamental new information about the interaction of nuclei in the hindbrain. These systems can be dissected anatomically, functionally and pharmacologically. The analysis of these hindbrain nuclei will aid in elucidating the physiology and neurobiology underlying this hindbrain system and extend our knowledge of neural regulation of fluid and electrolyte balance.